SUMMARY / RELATED TOPICS

Bradykinin

Bradykinin is an inflammatory mediator. It is a peptide that causes blood vessels to dilate via the release of prostacyclin, nitric oxide, Endothelium-Derived Hyperpolarizing Factor. Bradykinin is a physiologically and pharmacologically active peptide of the kinin group of proteins, consisting of nine amino acids. A class of drugs called angiotensin converting enzyme inhibitors increase bradykinin levels by inhibiting its degradation, thereby increasing its blood pressure lowering effect. ACE inhibitors are FDA approved for the treatment of heart failure. Bradykinin is a 9-amino acid peptide chain; the amino acid sequence of bradykinin is: Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg. Its empirical formula is therefore C50H73N15O11; the kinin-kallikrein system makes bradykinin by proteolytic cleavage of its kininogen precursor, high-molecular-weight kininogen, by the enzyme kallikrein. Moreover, there is compelling evidence that plasmin, a fibrinolytic enzyme, is able to generate bradykinin after HMWK cleavage.

In humans, bradykinin is broken down by three kininases: angiotensin-converting enzyme, aminopeptidase P, carboxypeptidase N, which cleave the 7-8, 1-2, 8-9 positions, respectively. Bradykinin is a potent endothelium-dependent vasodilator and mild diuretic, which may cause a lowering of the blood pressure, it causes contraction of non-vascular smooth muscle in the bronchus and gut, increases vascular permeability and is involved in the mechanism of pain. During inflammation, it is released locally from mast basophils during tissue damage. In relation to pain, bradykinin has been shown to sensitize TRPV1 receptors, thus lowering the temperature threshold at which they activate, thus contributing to allodynia. Initial secretion of bradykinin post-natally causes constriction and eventual atrophy of the ductus arteriosus, forming the ligamentum arteriosum between the pulmonary trunk and aortic arch, it plays a role in the constriction and eventual occlusion of a number of other fetal vessels, including the umbilical arteries and vein.

The differential vasoconstriction of these fetal vessels compared to the vasodilator response of other vessels suggest that the walls of these fetal vessels are different than other vessels. The B1 receptor is expressed only as a result of tissue injury, is presumed to play a role in chronic pain; this receptor has been described to play a role in inflammation. Most it has been shown that the kinin B1 receptor recruits neutrophil via the chemokine CXCL5 production. Moreover, endothelial cells have been described as a potential source for this B1 receptor-CXCL5 pathway; the B2 receptor participates in bradykinin's vasodilatory role. The kinin B1 and B2 receptors belong to G protein coupled receptor family. Bradykinin is thought to be the cause of the dry cough in some patients on prescribed angiotensin-converting enzyme inhibitor drugs, it is thought that bradykinin is converted to inactive metabolites by ACE, therefore inhibition of this enzyme leads to increased levels of bradykinin. Bradykinin may mediate a local release of histamine.

In severe cases, the elevation of bradykinin may result in a medical emergency. People of African descent have up to 5x increased risk of ACE inhibitor induced angioedema due to hereditary predisposing risk factors such as hereditary angioedema; this refractory cough is a common cause for stopping ACE inhibitor therapy. Overactivation of bradykinin is thought to play a role in a rare disease called hereditary angioedema known as hereditary angio-neurotic edema. A bradykinin-potentiating factor which increases both the duration and magnitude of the effects of bradykinin on vasodilation and the consequent fall in blood pressure, was discovered in Bothrops jararaca venom. On the basis of this finding, a non-protein analog of BPF, effective orally was developed: the first angiotensin converting enzyme inhibitor captopril, it was approved by the FDA for the treatment of hypertension in 1981. Bradykinin inhibitors are being developed as potential therapies for hereditary angioedema. Icatibant is one such inhibitor.

Additional bradykinin inhibitors exist. It has long been known in animal studies that bromelain, a substance obtained from the stems and leaves of the pineapple plant, suppresses trauma-induced swelling caused by the release of bradykinin into the bloodstream and tissues. Other substances that act as bradykinin inhibitors include aloe and polyphenols, substances found in red wine and green tea. Bradykinins have been implicated in a number of cancer progression processes. Increased levels of bradykinins resulting from ACE inhibitor use have been associated with increased lung cancer risks Bradykinins have been implicated in cell proliferation and migration in gastric cancers, bradykinin antagonists have been investigated as anti-cancer agents. Bradykinin was discovered in 1948 by three Brazilian physiologists and pharmacologists working at the Instituto Biológico, in São Paulo, led by Dr. Maurício Rocha e Silva. Together with colleagues Wilson Teixeira Beraldo and Gastão Rosenfeld, they discovered the powerful hypotensive effects of bradykinin in animal preparations.

Bradykinin was detected in the blood plasma of animals after the addition of venom extracted from the Bothrops jararaca

Madeleine Tribolati

Madeleine Tribolati was a pioneering French trade unionist. She is remembered for her work during the 1936 negotiation of collective agreements, demanding equal professional rights for men and women and upholding the principle "for equal work, equal pay". After the Second World War, in 1946 she became deputy general secretary of the French Employees Federation and in 1948, vice-president of the French Confederation of Christian Workers. Born in Paris on 23 March 1905, Madeleine Tribolati was the daughter of a labourer and a cleaning woman. Although she attended a secular state school, she became attracted to Catholicism. After starting to work when she was 13, she learnt about how women's trade unions offered women opportunities to defend their rights. In 1924, she joined the French Confederation of Christian Workers and attended a training course at the École Normale Sociale where over the next three years she learnt about church doctrine, labour law and trade unions with a view to entering the teaching profession.

In the late 1920s, she began to work as a shorthand-typist and in 1931 was elected to the board of the Union of Shorthand-Typists. She served as a youth delegate for the CFTC, chairing a number of youth meetings until 1935 when she joined the board of the Employees Federation. During this period, she contributed a number of articles to the union periodicals La Travailleuse and Syndicalisme, commenting on conditions for working mothers and housewives and emphasizing a woman's right to work with the slogan "à rendement égal, salaire égal", her conclusions were used in a report she presented to the women's meeting before the CFTC's 16th congress when they were taken into consideration. Her success in convincing women delegates from the CGT to back her proposals on "the female condition" surprised the male delegates in view of the hostile relations between the CGT and the CFTC. After the war, in 1946 she was once again elected as the Employees Federation's deputy general secretary and at the 14th congress of the CFTC in 1948, she became the organization's vice-president.

In 1965, she again was elected vice-president of the CFTC, succeeding in obtaining generalization of supplementary pensions in 1972. She retired in 1975. Madeleine Tribolati died in Paris on 25 October 1995

Mikhail Svechnikov

Mikhail Stepanovich Svechnikov was a Russian military officer in the Imperial Russian Army and the Red Army. He is best known as one the military leaders of the Red Guards in the 1918 Finnish Civil War. After his service in the Imperial Russian Army, Svechnikov took part at the 1917 October Revolution. During the 1918 Finnish Civil War he worked as a military advisor for the Red Guards. In February 1918, Svechnikov was shortly the Commander-in-Chief of the Northern Front, replaced by Hugo Salmela, he was the highest ranked Russian officer who joined the Finnish Red Guards. As the Finnish Civil War was over, Svechnikov fought in the Russian Civil War, in which he led the Caspian-Caucasian Front in the unsuccessful Northern Caucasus Operation. Since 1922 he worked as a military lecturer. In 1934 Svechnikov was transferred to the Frunze Military Academy, he was arrested in 1937, accused on "Fascist conspiracy", executed at the Kommunarka shooting ground in Moscow. Svechnikov was rehabilitated after Stalin's death in 1956